Birdshot Chorioretinopathy : Prospective Follow-up and Immunogenetic Studies(CO-BIRD)

Overview

The purpose of this study is twofold: 1. To analyze the clinical features of a cohort of patients with birdshot chorioretinopathy (BCR), an inflammatory bilateral ocular disease, affecting the choroid and the retina. Various imaging techniques will be used to assess the effect of the disease on the retina and the choroid. A standardized assessment of the visual function will be performed with visual acuity, visual field and color vision testing. The quality of life of the patients will be evaluated with the VFQ-25 questionnaire. These analyses will help delineating different forms of the disease among its heterogeneous presentations. 2. To identify predisposing factors for the disease. The condition is unique from the immunogenetic standpoint by its association with the HLA-A29 allele, which is the strongest link between an HLA class I antigen and a disease. To date, however, the mechanisms leading to birdshot chorioretinopathy remain unknown. GWAS (Genome Wide association Study) based on DNA of the cohort patients will be performed with the aim to identify other susceptibility genes associated with BCR.

Birdshot chorioretinopathy is a bilateral chronic posterior uveitis that has been named in 1980. The "birdshot lesions" are the hallmark of the disease. In their most typical aspect these lesions are ovoid shaped hypopigmented spots at the level of the choroid. One of the main difficulties of the diagnosis lies in the spectrum of presentations of the disease. The typical birdshot lesions are ovoid with their main axis oriented toward the optic disc. However, some are round and the can be clearly seen on fundus examination while others can be limited to subtle depigmentations. Typical lesions are one-quarter to one-half disc diameters, but confluent lesions may yield larger areas of depigmentation that are difficult to recognize. Although the typical lesions are depigmented, their presentation may change over time and pigment or atrophy may replace the initial cream-colored spots. The typical location, or the most easily seen location of the spots, is nasal to the optic disc. However, involvement of the posterior pole inside the temporal arcade is also possible. The spots usually predominate in the mid-periphery, but may also extend to the equator. A standardized classification of the birdshot lesions according to their size, their number, their pigmentation and their localization has been suggested to help in the categorization of the various disease presentations and for the longitudinal follow-up of affected patients. Spots clearly visible at the time of the diagnosis may disappear later. Hence, if the diagnosis of the birdshot chorioretinopathy is not made when spots are clearly visible, later presentations may not meet the definition commonly used for the disease. The disappearance of birdshot spots after treatment has been documented, but the effect of treatment on spots has not yet been assessed in large cohorts of patients. Indocyanine green angiography has been suggested as a reliable method to detect spots. However, it remains to be validated by a randomized assessment comparing indocyanine green angiography to color photographs for the detection of birdshot lesions. Fluorescein angiography is useful in patients with birdshot chorioretinopathy to assess disease activity. In active disease, angiographic findings include leakage of the retinal veins, macular edema and optic disk hyperfluorescence. These findings are not disease specific, but they require a careful examination of the fundus seeking subtle spots when birdshot lesions are not obvious. Given the above, the first goal of our prospective cohort study is to assess the heterogeneity of the disease, its spectrum of presentation and its evolution over time. One of the characteristics of birdshot chorioretinopathy is its association with the HLA-A29 allele, which constitutes the strongest link between a disease and class I HLA allele. The mechanism by which HLA-A29 confers a risk for birdshot chorioretinopathy is a key question that remains unanswered. As with other associations between HLA class I antigens and diseases (HLA-B27 with spondylarthropathies and HLA B51 with Behçet's disease), the physiopathogeny of these links have not been elucidated. Other factors playing a role in the physiopathogeny of the disease and not linked to the major histocompatibility complex are researched. A few families of patients with birdshot chorioretinopathy have been reported, which could point to additional genetic factors for disease susceptibility but does not rule out an environmental effect. Hence, the complex physiopathology of birdshot chorioretinopathy could involve the HLA-A29 allele, other unknown genetic factors, as well as environmental factors. Given the above, we are planning a GWAS (Genome Wide association Study) based on DNA of the cohort patients, which will be performed with the aim to identify other susceptibility genes associated with BCR.